US10092858B2ActiveUtilityA1

Method and apparatus for improved resolution chromatography

64
Assignee: RITCHIE HARALDPriority: May 25, 2012Filed: May 25, 2012Granted: Oct 9, 2018
Est. expiryMay 25, 2032(~5.9 yrs left)· nominal 20-yr term from priority
Inventors:Harald RitchieRoss Andrew Shalliker
G01N 30/60G01N 30/603B01D 15/22B01D 15/18B01D 15/10G01N 30/6017G01N 30/6086G01N 30/6004
64
PatentIndex Score
2
Cited by
35
References
39
Claims

Abstract

An apparatus and a method are provided for column chromatography, which provide improvements in separation resolution and detection sensitivity, comprising a chromatography column having an inlet and an outlet, wherein the inlet is configured to introduce a flow of mobile phase into the column carrying a sample, wherein the inlet is further configured to introduce the flow of mobile phase into the column in at least two separate portions which are independently controllable, and to introduce the portions into different radial regions of the column, such that the portions flow longitudinally through the column in different radial regions. The sample preferably is contained in one of the portions, especially a central portion, in a higher concentration than in the other portion(s). Preferably the flow velocities of the portions are independently controllable.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. An apparatus for column chromatography, comprising:
 a chromatography column having an inlet assembly; 
 the inlet assembly including:
 an outer surface; 
 a plurality of inlet ports comprising, at least one central inlet port and at least one peripheral inlet port; and, 
 an inlet frit assembly including: 
 a plurality of separate porous frit sections comprising a central frit section adapted to receive fluid from the at least one central inlet port and an annularly surrounding concentric frit section adapted to receive fluid from the at least one peripheral inlet port, wherein the annularly surrounding concentric frit section is separated from the central frit section by a non-porous flow barrier, whereby mobile phase entering any one of the porous frit sections is prevented from laterally flowing into an adjacent frit section by the non-porous flow barrier; 
 wherein the at least one central inlet port and the at least one peripheral inlet port extend from the outer surface of the inlet assembly to the central frit section and to the annularly surrounding concentric frit section respectively; 
 
 wherein the inlet assembly has a first solvent delivery system fluidically coupled with the at least one central inlet port and a second solvent delivery system coupled with the at least one peripheral inlet port. 
 
     
     
       2. The apparatus of  claim 1 , wherein a sample is introduced onto the chromatography column via at least one sample source, the sample being introduced onto the chromatography column through any one of the plurality of separate porous frit sections. 
     
     
       3. The apparatus of  claim 1 , wherein a sample is introduced onto the chromatography column in two different sample portions, each sample portion being introduced onto the chromatography column through a different one of the plurality of inlet ports. 
     
     
       4. The apparatus of  claim 1 , wherein a first portion of mobile phase is introduced into a central radial region of the chromatography column via the central frit section and a second portion of mobile phase is introduced into a peripheral radial region of the chromatography column located radially outwards of and annularly surrounding the central radial region of the chromatography column via the annularly surrounding concentric frit section. 
     
     
       5. The apparatus of  claim 4 , wherein the central radial region of the chromatography column is a region located substantially on a central axis running through the chromatography column from the inlet assembly to an outlet assembly. 
     
     
       6. The apparatus of  claim 4 , wherein a sample is contained in the first portion of mobile phase in a higher concentration than in the second portion of mobile phase. 
     
     
       7. The apparatus of  claim 6 , wherein the sample is substantially contained in the first portion of mobile phase. 
     
     
       8. The apparatus of  claim 4 , wherein the second portion of mobile phase constrains a migration of a sample from the first portion of mobile phase toward a wall of the chromatography column as the sample progresses towards an outlet of the chromatography column. 
     
     
       9. The apparatus of  claim 4 , wherein the first portion of mobile phase and the second portion of mobile phase have substantially the same flow velocity. 
     
     
       10. The apparatus of  claim 1 , wherein the chromatography column has an inlet flow distributor inside the inlet assembly to convey at least two separate portions of mobile phase in separate channels therein. 
     
     
       11. The apparatus of  claim 10 , wherein the inlet flow distributor is a separate part which is fitted inside the inlet assembly. 
     
     
       12. The apparatus of  claim 10 , wherein the inlet flow distributor comprises a first set of at least one channel arranged such that in use the first set lies in a first radial region of the chromatography column to convey a first portion of the mobile phase to a first radial region of the chromatography column and a second set of at least one channel arranged such that in use the second set lies in a second radial region of the chromatography column to convey a second portion of the mobile phase to a second radial region of the chromatography column. 
     
     
       13. The apparatus of  claim 12 , wherein the first radial region of the chromatography column in which the first set lies is a central radial region and the second radial region of the chromatography column in which the second set lies is a peripheral radial region of the chromatography column located radially outward of the central radial region. 
     
     
       14. The apparatus of  claim 12 , wherein the inlet flow distributor comprises one central channel in the first set and from two to ten outer channels in the second set. 
     
     
       15. The apparatus of  claim 1 , wherein the mobile phase leaves the chromatography column as a flow of eluate to be processed as a single portion of eluate. 
     
     
       16. The apparatus of  claim 2 , wherein mobile phase leaves the chromatography column as a flow of eluate and an outlet assembly is configured to split the flow of eluate as it leaves the chromatography column through the outlet assembly into at least two separate portions of eluate. 
     
     
       17. The apparatus of  claim 16 , wherein the outlet assembly is configured to direct a first portion of the eluate to a first processing means and a second portion of the eluate to a second processing means separate to the first processing means. 
     
     
       18. The apparatus of  claim 16 , wherein the at least two separate portions of eluate emanate from different radial regions of the chromatography column. 
     
     
       19. The apparatus of  claim 18 , wherein a first portion of eluate emanates from a central radial region of the chromatography column and a second portion of eluate emanates from a peripheral radial region of the chromatography column located radially outwards of the central radial region. 
     
     
       20. The apparatus of  claim 16 , wherein one portion of eluate is 50% or less, of a total volume of eluate. 
     
     
       21. The apparatus of  claim 16 , wherein the outlet assembly is provided with an outlet frit assembly configured to split the flow of eluate into the at least two separate portions of eluate. 
     
     
       22. The apparatus of  claim 21 , wherein the outlet frit assembly comprises at least two separate porous frit sections, separated by a non-porous flow barrier. 
     
     
       23. The apparatus of  claim 22 , wherein the outlet frit assembly comprises a plurality of separate porous frit sections comprising a central frit section and at least one surrounding concentric frit section, wherein each surrounding concentric frit section is separated from adjacent frit sections by a non-porous flow barrier, whereby mobile phase entering any one of the porous frit sections is prevented from laterally flowing into an adjacent frit section by the non-porous flow barrier. 
     
     
       24. The apparatus of  claim 16 , wherein the chromatography column has an outlet flow distributor in the outlet assembly to convey the at least two separate portions of the eluate flow in separate channels therein. 
     
     
       25. The apparatus of  claim 24 , wherein the outlet flow distributor is a separate part which is fitted inside the outlet assembly of the chromatography column. 
     
     
       26. The apparatus of  claim 24 , wherein the outlet flow distributor comprises a first set of at least one outlet channel arranged such that in use the first set lies in a first radial region of the column to convey a first portion of eluate and a second set of at least one outlet channel arranged such that in use the second set lies in a second radial region of the chromatography column to convey a second portion of eluate. 
     
     
       27. The apparatus of  claim 26 , wherein the first radial region of the chromatography column in which the first set of at least one outlet channel lies is a central radial region and the second radial region of the column in which the second set of at least one outlet channel lies is a region located radially outward of the central radial region. 
     
     
       28. The apparatus of  claim 26 , wherein the outlet flow distributor comprises one central outlet channel in the first set and from two to ten outer outlet channels in the second set. 
     
     
       29. The apparatus of  claim 24 , wherein the outlet assembly is provided with an outlet frit assembly configured to split the flow of eluate into the at least two separate portions, the outlet frit assembly comprising at least two separate frit sections, which are separated by a non-porous flow barrier wherein the flow distributor is in contact with the non-porous flow barrier of the frit assembly so that the non-porous flow barrier of the outlet frit assembly provides a seal between the outlet frit and the outlet flow distributor thereby sealing adjacent portions of eluate flow from each other. 
     
     
       30. The apparatus of  claim 16 , comprising a detector arranged to detect at least one portion of the eluate separately from the other portion or portions of the eluate. 
     
     
       31. The apparatus of  claim 16 , comprising a fraction collector arranged to collect fractions of at least one portion of the eluate separately from the other portion or portions of the eluate. 
     
     
       32. The apparatus of  claim 30 , wherein the detector is arranged to separately detect a portion of the eluate which has emanated from a central radial region of the chromatography column. 
     
     
       33. The apparatus of  claim 31 , wherein the fraction collector is arranged to separately collect fractions of a portion of the eluate which has emanated from a central radial region of the column. 
     
     
       34. The apparatus of  claim 16 , wherein one of the portions of eluate emanates from a peripheral radial region of the chromatography column and is substantially free from at least one sample that has been introduced onto the chromatography column via the at least one sample source. 
     
     
       35. The apparatus of  claim 34 , wherein the apparatus is configured to re-use the portion of eluate which emanates from a peripheral radial region in further chromatography. 
     
     
       36. The apparatus of  claim 16 , wherein the apparatus comprises at least first and second processing means for separately processing the at least two separate portions of eluate, wherein the first and second processing means each independently comprise one or more of: a detector, a waste reservoir, a fraction collector and a column inlet. 
     
     
       37. The apparatus of  claim 4 , wherein the first portion of the mobile phase and the second portion of the mobile phase have both flow velocities and sample concentrations that are independently controllable. 
     
     
       38. The apparatus of  claim 1 , wherein the first solvent delivery system and the second solvent delivery system are from a common solvent pump or wherein the first solvent delivery system and the second solvent delivery system are from two separate solvent pumps. 
     
     
       39. The apparatus of  claim 1 , wherein the inlet assembly has a first sample source coupled with the at least one central inlet port.

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